PROJECT SUMMARY/ABSTRACT We apply for renewal of a T32 postdoctoral training program to support 5 postdoctoral trainees studying molecular mechanisms of immunologic tolerance and autoimmunity. Training faculty include a highly interactive group of 28 faculty (among about 70 immunologists and principal investigators in our community) strongly focused on B and T cell development, antigen recognition, repertoire development, silencing by editing, deletion and anergy, and strategies to enhance immunity to tumors. Training is performed at the University of Colorado (UC) and its affiliate National Jewish Health (NJH). All trainers are primary or secondary members of the Department of Immunology & Microbiology and members of the Immunology graduate Program at UC. The number of faculty on this application have increased by 40% since our last competitive renewal, prompting us to increase our request for trainee support from 4 to 5. The increase in faculty reflects recruitment of new faculty to our institution and broadening in areas in which we intend to train, such as tumor immunology and translational research. The program is headed by two Program Directors, Dr. Roberta Pelanda, who has become the co-director in 2017 and will be the primary grant contact, and Dr. John Cambier, who has directed the Program since its inception. These co-directors have expertise in immunological tolerance and autoimmunity with studies in both mice and humans. Dr. Pelanda is also the Director of the hematopoietic humanized mouse core facility, while Dr. Cambier has trained more than 60 postdocs and graduate students, and is a Distinguished Professor and Chairman of the Department of Immunology and Microbiology and the Director of the UCSOM Human Immunology and Immunotherapy Initiative. Postdoctoral fellows will be selected for support by the Recruitment and Appointing Committee after application by the trainee and mentor. Selection will be based on merit and research proposed. Trainees will be required to take a course in the Responsible Conduct in Research, to attend and present once a year in our weekly ?Research in Progress? forum, and to complete each year an Individual Development Plan. Evaluation of progress of research and career guidance will be provided by a mentoring committee consisting of at least 3 faculty members and meeting with the trainee once every 6 months. The goal of this training program is to provide fellows with comprehensive knowledge of immune tolerance and mouse models of autoimmunity, and sufficient understanding of clinical autoimmunity to enable their development of productive clinical collaborative ties for translation of research. This Training Program continues to be a major focus for immunological research in the Rocky Mountain region in particular and the USA in general.